rs45540831

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.3153G>A (p.Ala1051=) variant in the MYH7 gene is 0.68% (490/66740) of European chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; PMID:29300372). LINK:https://erepo.genome.network/evrepo/ui/classification/CA013398/MONDO:0004994/002

Frequency

Genomes: 𝑓 0.0052 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 57 hom. )

Consequence

MYH7
NM_000257.4 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:25

Conservation

PhyloP100: -3.91

Publications

5 publications found

Variant links:

Genes affected

MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]

MYH7 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dilated cardiomyopathy 1S
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
MYH7-related skeletal myopathy
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
myopathy, myosin storage, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
myopathy, myosin storage, autosomal dominant
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
congenital myopathy 7A, myosin storage, autosomal dominant
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Ebstein anomaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hyaline body myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
left ventricular noncompaction
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

MYH7 links:

ENSG00000294572 (HGNC:):

ENSG00000294572 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000257.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7	NM_000257.4	MANE Select	c.3153G>A	p.Ala1051Ala	synonymous	Exon 25 of 40	NP_000248.2	P12883
	MYH7	NM_001407004.1		c.3153G>A	p.Ala1051Ala	synonymous	Exon 24 of 39	NP_001393933.1	P12883

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYH7	ENST00000355349.4	TSL:1 MANE Select	c.3153G>A	p.Ala1051Ala	synonymous	Exon 25 of 40	ENSP00000347507.3	P12883
MYH7	ENST00000858540.1		c.3153G>A	p.Ala1051Ala	synonymous	Exon 25 of 40	ENSP00000528599.1
MYH7	ENST00000965955.1		c.3153G>A	p.Ala1051Ala	synonymous	Exon 25 of 40	ENSP00000636014.1

Frequencies

GnomAD3 genomes

AF:

0.00524

AC:

798

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00529

AC:

1330

AN:

251484

AF XY:

0.00553

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00934

Gnomad OTH exome

AF:

0.00521

GnomAD4 exome

AF:

0.00838

AC:

12251

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00831

AC XY:

6040

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33478

American (AMR)

AF:

0.00145

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00410

AC:

354

AN:

86256

European-Finnish (FIN)

AF:

0.00183

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00417

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0101

AC:

11250

AN:

1112010

Other (OTH)

AF:

0.00667

AC:

403

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

781

1561

2342

3122

3903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

400

800

1200

1600

2000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00522

AC:

795

AN:

152306

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

327

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

41558

American (AMR)

AF:

0.00111

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0100

AC:

680

AN:

68032

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

121

161

201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.174

Hom.:

6615

Bravo

AF:

0.00536

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.00942

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (11)

not provided (6)

Cardiomyopathy (2)

Hypertrophic cardiomyopathy 1 (2)

Cardiovascular phenotype (1)

Hypertrophic cardiomyopathy (1)

MYH7-related skeletal myopathy (1)

Myosin storage myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.2

(source)

DANN

Benign

0.88

PhyloP100

-3.9

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over